title: The persistence of a long-term negative affective state following the induction of either acute or chronic pain.
abstract: Clinically, pain is a complex phenomenon consisting of both sensory and affective aberrations that can persist indefinitely. Pre-clinically, several animal paradigms have been established that reliably mimic both the acute and chronic aspects of pain pertinent to the human condition; however, the commonly used behavioral models only assess the sensory component of pain elicited by an evoked nociceptive stimulus. Since the affective-motivational component of pain is an important determinant of the overall pain experience in man, we investigated how this aspect may be modeled long-term in rats using novel objects and a modified conditioned place aversion (CPA) paradigm. Findings demonstrate that animals subjected to either neuropathic injury or inflammatory insult display a significant conditioned place aversion to a pain-paired environment that is paralleled by an increased number of hind paw withdrawals and fewer number of novel object interactions during painful conditioning sessions. Moreover, this aversion is maintained for 1 month in the absence of further conditioning. We also determined that a non-analgesic, non-rewarding dose of morphine administered prior to pain-paired conditioning sessions attenuates the pain-induced aversion and its relative persistence in both pain models. Together, these findings underscore the importance of negative affect accompanying painful conditions and its long-term persistence even when the injury or insult has resolved. Lastly, these results suggest how both sensory and affective aberrations associated with neuropathic- and inflammatory-like conditions and the memory of such known to impact quality of life in man may be addressed pre-clinically in rodents.
authors.affiliation: Neuroscience Discovery Research, Wyeth Research, CN 8000, Princeton, NJ 08543, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Hummel
authors.forename: Peimin
authors.initials: P
authors.lastname: Lu
authors.forename: Terri A
authors.initials: TA
authors.lastname: Cummons
authors.forename: Garth T
authors.initials: GT
authors.lastname: Whiteside
mesh_terms: D000208:Acute Disease / Q000523:psychology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001008:Anxiety Disorders / Q000209:etiology / Q000503:physiopathology / Q000523:psychology*; D001362:Avoidance Learning / Q000502:physiology; D002351:Carrageenan; D002908:Chronic Disease / Q000523:psychology; D003213:Conditioning, Psychological / Q000502:physiology; D003866:Depressive Disorder / Q000209:etiology / Q000503:physiopathology / Q000523:psychology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology / Q000523:psychology; D018836:Inflammation Mediators; D019964:Mood Disorders / Q000209:etiology / Q000503:physiopathology / Q000523:psychology*; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000150:complications / Q000503:physiopathology / Q000523:psychology*; D051381:Rats; D013315:Stress, Psychological / Q000209:etiology / Q000503:physiopathology / Q000523:psychology*; D013995:Time
chemical_list: D000701:Analgesics, Opioid; D018836:Inflammation Mediators; D009020:Morphine; D002351:Carrageenan